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Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

ABSTRACT: Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.

SUBMITTER: Ebneter A

PROVIDER: S-EPMC4361633 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

Ebneter Andreas A Agca Cavit C Dysli Chantal C Zinkernagel Martin S MS

PloS one 20150316 3

Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using ...[more]

PMID: 25775456

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Project description:PurposeTo examine whether deep-learning denoised optical coherence tomography angiography (OCTA) images could enhance automated macular ischemia quantification in branch retinal vein occlusion (BRVO).MethodsThis retrospective, single-center, cross-sectional study enrolled 74 patients with BRVO and 46 age-matched healthy subjects. The severity of macular ischemia was graded as mild, moderate, or severe. Denoised OCTA images were produced using a neural network model. Quantitative parameters derived from denoised images, including vessel density and nonperfusion area, were compared with those derived from the OCTA machine. The main outcome measures were correlations between quantitative parameters, and areas under receiver operating characteristic curves (AUCs) in classifying the severity of the macular ischemia.ResultsThe vessel density and nonperfusion area from denoised images were correlated strongly with the corresponding parameters from machine-derived images in control eyes and BRVO eyes with mild or moderate macular ischemia (all P < 0.001). However, no such correlation was found in eyes with severe macular ischemia. The vessel density and nonperfusion area from denoised images had significantly larger area under receiver operating characteristic curve than those derived from the original images in classifying moderate versus severe macular ischemia (0.927 vs 0.802 [P = 0.042] and 0.946 vs 0.797, [P = 0.022], respectively). There were no significant differences in the areas under receiver operating characteristic curve between the denoised images and the machine-derived parameters in classifying control versus BRVO, and mild versus moderate macular ischemia.ConclusionsA neural network model is useful for removing speckle noise on OCTA images and facilitating the automated grading of macular ischemia in eyes with BRVO.Translational relevanceDeep-learning denoised optical coherence tomography angiography images could enhance automated macular ischemia quantification.

Project description:PURPOSE:To examine the relationship between optical coherence tomography (OCT) images and clinical course in eyes with branch retinal vein occlusion (BRVO) treated with intravitreal ranibizumab injection (IVR). DESIGN:Prospective cohort study. PARTICIPANTS:Thirty eyes of 30 patients with BRVO treated with IVR. METHODS:All patients received 1 initial IVR followed by repeated injections in the pro re nata (PRN) regimen. Correlations between logarithm of minimum angle of resolution best-corrected visual acuity (logMAR BCVA) or number of IVRs after 12 months and OCT parameters including the external limiting membrane (ELM), ellipsoid zone (EZ), interdigitation zone (IZ), and photoreceptor outer segment (PROS) length at first resolution of macular edema (ME) were assessed. Resolution of ME was defined as central foveal thickness <300 ?m and the absence of subretinal fluid. OCT parameters influencing BCVA and number of IVRs were evaluated using multivariate analysis. Correlations between nonperfusion areas (NPAs) and thinning areas and changes in retinal thickness of BRVO-affected areas were assessed. RESULTS:Of the 30 patients, 27 completed this study and were included in the statistical analyses. The mean logMAR BCVA at 3, 6, and 12 months was 0.16 ± 0.19, 0.09 ± 0.20, and 0.07 ± 0.20, respectively, which improved significantly from baseline at each visit (p < 0.0001, respectively), while the mean number of IVRs at 12 months was 3.9 ± 2.2. The mean number of IVRs for the first resolution of ME was 1.6 ± 0.8. Eyes with ELM and EZ defects at the points of first resolution of ME were correlated with a significantly lower BCVA at 12 months compared with eyes with preserved ELMs and EZs (p = 0.035, p = 0.002, respectively). However, eyes with IZ defects at the points of first resolution of ME were not correlated with a significantly lower BCVA at 12 months compared with eyes with preserved IZs (p = 0.160). Defects in the EZ at the points of first resolution of ME significantly affected the number of IVRs at 12 months (p = 0.042), although the ELM and IZ did not. PROS length at the points of first resolution of ME was significantly correlated with BCVA and number of IVRs at 12 months (p = 0.006, p = 0.0008, respectively). In multivariate analysis, PROS length at the points of first resolution of ME had the most significant effect on BCVA and number of IVRs (p = 0.013, p = 0.012, respectively). NPA size on fluorescein angiography and thinning area on OCT within the macular area showed a significant correlation (p = 0.003, r = 0.971). The retinal thickness of ischemic BRVO-affected areas was significantly less than that of control areas at 10, 11, and 12 months (p = 0.001, p = 0.005, p = 0.003, respectively). CONCLUSION:We showed that the 1+PRN regimen may be a useful therapy for ME due to BRVO. In addition, PROS length at points of first resolution of ME appears to be a good indicator of BCVA and number of IVRs in BRVO patients.

Project description:PurposeTo determine the impact of segmentation error correction and precision of standardized grading of time domain optical coherence tomography (OCT) scans obtained during an interventional study for macular edema secondary to central retinal vein occlusion (CRVO).MethodsA reading center team of two readers and a senior reader evaluated 1199 OCT scans. Manual segmentation error correction (SEC) was performed. The frequency of SEC, resulting change in central retinal thickness after SEC, and reproducibility of SEC were quantified. Optical coherence tomography characteristics associated with the need for SECs were determined. Reading center teams graded all scans, and the reproducibility of this evaluation for scan quality at the fovea and cystoid macular edema was determined on 97 scans.ResultsSegmentation errors were observed in 360 (30.0%) scans, of which 312 were interpretable. On these 312 scans, the mean machine-generated central subfield thickness (CST) was 507.4 ± 208.5 μm compared to 583.0 ± 266.2 μm after SEC. Segmentation error correction resulted in a mean absolute CST correction of 81.3 ± 162.0 μm from baseline uncorrected CST. Segmentation error correction was highly reproducible (intraclass correlation coefficient [ICC] = 0.99-1.00). Epiretinal membrane (odds ratio [OR] = 2.3, P < 0.0001), subretinal fluid (OR = 2.1, P = 0.0005), and increasing CST (OR = 1.6 per 100-μm increase, P < 0.001) were associated with need for SEC. Reading center teams reproducibly graded scan quality at the fovea (87% agreement, kappa = 0.64, 95% confidence interval [CI] 0.45-0.82) and cystoid macular edema (92% agreement, kappa = 0.84, 95% CI 0.74-0.94).ConclusionsOptical coherence tomography images obtained during an interventional CRVO treatment trial can be reproducibly graded. Segmentation errors can cause clinically meaningful deviation in central retinal thickness measurements; however, these errors can be corrected reproducibly in a reading center setting.Translational relevanceSegmentation errors are common on these images, can cause clinically meaningful errors in central retinal thickness measurement, and can be corrected reproducibly in a reading center setting.

Dataset Information

Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

Publications

Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

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